Abstract
Chronic oral toxicity studies are generally conducted in dogs and rats according to methods described by Fitzhugh(1). Such methodology, while noting that dietary effects on the toxicity of chemicals represent a problem, does not prescribe the use of specific standardized diets. “Proved commercial diets” are usually employed and the composition of such diets varies considerably.
In the case of a relatively weak hepatic carcinogen such as Safrole (2,3,4,5), dietary composition may have significant bearing on the outcome of experiments, and a study was therefore made to determine hepatotoxic effects of Safrole as well as those of a more potent hepatic carcinogen, butter yellow, in rats placed on diets containing 5, 10 and 30% protein. Fat content was varied to 5 and 15% in the case of the 30% diet. One group of rats was also fed a riboflavin-free 10% protein, 5% fat diet to compare the butter yellow-carcinogenesis-enhancing effect of this deficiency with its effect on Safrole carcinogenesis.
Material, methods and experimental design. The animals used were Osborne-Mendel male rats obtained from Camm Research Institute. Animals received Achromycin†† (0.001%) in drinking water for three days on arrival. Starting weight averaged 114 g (range, 92–135 g) for each group of 10 rats. Food consumption measurements were made during the first year of the experiment. The animals were given 0.5% Safrole† or 0.06% butter yellow mixed in their diet. The evaporation rate of Safrole was found by chemical analysis to be 11.3% per 3-day period(3). The diets were prepared in 2-kg lots as needed, kept refrigerated in sealed jars, and fed freshly every third day. All animals were kept individually in hanging cages. Animal room temperature was 24°C (± 2°C), and tap water was given ad libitum. All rats were killed when they appeared to be moribund.
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